Venetoclax Basket Trial for High Risk Hematologic Malignancies

Inclusion Criteria Cohort A Inclusion Criteria: * MDS, AML arising from MDS (MDS/AML), therapy related myeloid neoplasm (tMDS/AML) meeting at least one of the following criteria: * MDS with excess blasts (\>10%) * MDS with blasts \<10% with high-risk features * MDS refractory to initial treatment * Relapsed MDS * MDS/AML: May be newly diagnosed or relapsed/refractory disease. * Therapy related myeloid neoplasm (tMDS/AML): May be initial or relapsed/refractory disease. * Note: MDS or MDS/AML may be derived from a germline predisposition to myeloid malignancy as long as that condition does not confer increased toxicity to treatment. * Age ≤ 40 years of age, except the following subjects that must be \<18 years to enroll * Subjects with MDS/AML that have not received prior therapy * Subjects enrolled onto Dose level -2. * Lansky/Karnofsky performance status ≥ 50% * Participants must have fully recovered from the acute toxic effects of all and meet all of the following criteria: * Myelosuppressive chemotherapy: 14 days, or 5 half-lifes (whichever is shorter) must have elapsed since the completion of myelosuppressive therapy. Individuals may have received any of the following medications without a "wash-out" period * Standard maintenance therapy: dexamethasone/prednisone, vincristine, 6MP, low dose methotrexate) * Hydroxyurea * Intrathecal chemotherapy with methotrexate, hydrocortisone and/or cytarabine. * Radiation therapy (XRT): * …